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RIKEN Harima Institute Advanced Protein Crystallography Research Group Structurome Research Group Research Scientist: Tadashi Nakai |
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| P-protein's structure tells interesting stories | |
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As the building blocks of life, proteins are important information sources. Their structures can unlock doors to new understandings about current and past events. Studying their structures can also provide insights into human evolution and complex biological functions. A multi-laboratory team of researchers at RIKEN Harima Institute at SPring-8 illustrated this in the March 2005 issue of The EMBO Journal . They revealed the unique crystal structure of P-protein, or glycine decarboxylase, and showed how flaws in this building block damage processes within organism. P-protein is one of four proteins that participate in glycine degradation. While its structure was the last to be discovered, P-protein may be the most interesting. Its structure is unique. Before its structure was identified, P-protein mutations were implicated in non-ketotic hyperglycinemia, NKH, a phenomenon wherein glycine accumulates abnormally in the blood that is associated with several congenital neurological diseases. No effective treatment has yet been developed. Over 80% of people diagnosed with NKH have some mutation in the P-protein. With all four structures now revealed, studying the role of these structures in glycine degradation is possible and renews hopes for better therapies. Dr. Nakai and his colleagues identified the three-dimensional structure of P-protein for a type of heat-loving bacteria, Thermus thermophilus HB8. The P-protein of this bacteria shares many of the structural properties of human P-protein but can be more easily studied because of its heat-stable property. The structure has a novel tetramer formation, but is more like a bonding of two paired units, or dimers. Structure revealed, P-protein's molecular evolution unfolded to reveal the functional bases of its architecture. P-protein consists of asymmetric dimers, whereas all relatives of P-protein consist of symmetric dimers. This unique structure might have evolved from a symmetric ancestor so larger molecules could be processed by creating a roomier pocket within the P-protein structure to accommodate them. The structural asymmetry might also be triggered by functional changes within and between proteins and molecules to allow processes such as catalysing glycine degradation to occur. The structural knowledge also explains why mutations that create structural defects in P-protein decrease enzymatic activity, reduce glycine degradation and lead to disease. With so much revealed from one protein structure, more studies on protein structure-function relationships are expected. Some might tell as interesting a story as P-protein.
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